The requirements for the transformation of autoprothrombin III (Factor X) to autoprothrombin C (Factor Xa) can be met by using various substances and combinations of factors. Emphasis is placed on the use of natural substances rather than snake venoms, trypsin, and like substances. The enzyme structure seems to depend upon activation conditions, and chain separation and characterization are part of the work, as well as reactions with purified antithrombin III. One of the activators is tissue thromboplastin and the properties of the protein in that compound are being studied by chemical analysis. Thomboplastin and its components, as well as other procoagulants are programed for study with the use of the electron microscope. The same instrument is also being used to study (1) dissection and examination of selected parts of the vasculature from normal anesthetized dogs and donated human surgical specimens, (2) isolated hind limb perfusions, (3) preparation of plastic casts of various organ microcirculations, and (4) umbilical cord preparations. The aim is to learn about cellular participation in the thrombotic process. With the view of finding out more about the inception or acceleration of blood coagulation, the generation of Factor IXa activity is being studied in purified systems, as well as the effects of antigen-antibody reactions, and changes in the structure of fibrinogen. Part of the normal structure of fibrinogen is being studied. Components of fibronogen, thromboplastin, and other procoagulants where known ex vivo effects on blood enzymology or platelet aggregation are evident will be studied in in vivo models for effects on thrombosis and hemostasis.